Our studies have concerned regulation of gene expression during normal and abnormal differentiation processes. Hybridization, S1 mapping, and primer extension experiments demonstrated that the 2.2-kb and 1.7kb AFP mRNAs contain identical sequences from the eighth (G) exon to the 3' end of the 2.2-kb RNA but differ in sequences at the 5' end. The 1.7-kb RNA lacks sequence of the seven 5' exons present in the 2.2 kb RNA. However, this variant RNA contains additional sequences 5' to the G exon. The ts rat fetal hepatocytes grown at 40 degree C matured into the adult hepatocytes in the presence of glucocorticoid hormones. This was demonstrated by the inhibition of fetal gene but induction of adult gene expression by glucocorticoids. We have also demonstrated that adult liver produced an AFP mRNA which is indistinguishable from the 1.7 kb AFP mRNA. Glucocorticoids stimulated synthesis of the variant AFP encoded by the 1.7 kb RNA but did not enhance production of the corresponding mRNA. Expression of tyrosine amino transferase (TAT) gene in the ts adult hepatocyte line was ts and dependent upon the presence of glucocorticoid. cAMP alone was not sufficient to induce TAT gene expression, but it enhanced the induction by the steroid hormone. cDNAs encoding human placental pregnancy-specific beta1- glycoprotein (PSbetaG) have been isolated and characterized. Two cDNA clones (PSG16 and PSG93) differ only in sequence in the 3' end of the coding region. PSG93 contains an additional 86 bp at the end of the 3' coding region of PSG16. This insertion results in the generation of PSbetaG species of 418 amino acid residues instead of the 416 amino acid residues predicted by PSG16. These cDNA probes were used to study regulation of PSbetaG gene expression in human placental fibroblasts. We found that the PSbetaG synthesized by the fibroblasts was structurally different from placental PSbetaG.